OPTIC NEUROPATHY ASSOCIATED WITH COPPER DEFICIENCY AFTER GASTRIC BYPASS SURGERY Ankoor R. Shah, MD, Madhura A. Tamhankar, MD
Purpose: Patients undergoing gastric bypass procedures are predisposed to many vitamin and mineral deficiencies including copper, which can lead to optic neuropathy. Methods: A 35-year-old woman complained of progressive vision loss bilaterally 3 years after gastric bypass surgery (GBS). Results: Ophthalmic examination revealed the presence of subnormal visual acuity and pale optic nerves bilaterally. Laboratory testing showed copper deficiency. Complete improvement in vision was noted after copper was replenished. Conclusion: Nutritional deficiencies occurring after gastric bypass procedures are well reported. They happen and occur due to reduced gastric and enteral absorption and cause many systemic and neurologic manifestations. Optic neuropathy occurring after GBS is often due to vitamin B12 and folic acid deficiency. Copper deficiency causing systemic symptoms is very rare and usually takes decades to manifest. Our case is unique in that copper deficiency was noted as early as 3 years after GBS. Moreover rapid copper replenishment led to a dramatic recovery of vision. Our case underscores the need for maintaining high suspicion when evaluating patients with suspected optic neuropathy occurring after GBS since prompt diagnosis and treatment may lead to reversal of visual loss. RETINAL CASES & BRIEF REPORTS 8:73–76, 2014
lopathy, myopathy, and encephalopathy have been described3 that occur from nutritional deficiency of fatsoluble vitamins, folic acid, and zinc.4 Our patient, diagnosed with copper deficiency developed progressive visual decline 3 years after GBS. To the best of our knowledge, an early onset of copper deficiency as seen in our patient and a rapid recovery of vision noted after copper replenishment, have previously not been reported. Our case highlights the need for a high index of suspicion, which allows for prompt clinical diagnosis and treatment.
From the Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania.
O
besity is an epidemic in the United States with over 25% of adults and children clinically obese.1 The number of bariatric surgeries performed in the United States has steadily increased with 113,000 cases being performed annually.2 Patients who undergo gastric bypass surgery (GBS) are predisposed to many vitamin and mineral deficiencies secondary to gastric anatomical rearrangement. Numerous neurologic complications including polyneuropathy, mye-
Case Report Supported by Research to Prevent Blindness, Inc, New York, NY, that provided travel support. Paper presented as a poster at the North American NeuroOphthalmologic Society Meeting, San Antonio, TX, February 2012. None of the authors have any conflicting interests to disclose. Reprint requests: Madhura Tamhankar, MD, Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, 51 N. 39th Street, Philadelphia, PA 19104; e-mail: madhura. [email protected]
A 35-year-old woman presented with progressive systemic weakness, dizziness, and frequent falling over a 9-month period. One month before admission, the patient noted nausea, vomiting, peripheral edema without orthopnea, and lower extremity pain. Her medical history was significant for having undergone a Roux-en-Y GBS 3 years ago. She was taking an oral multivitamin before hospital admission. While in the hospital, the patient complained of progressively worsening vision bilaterally for 2 weeks. She denied night blindness. Her ocular history included ocular allergies treated
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RETINAL CASES & BRIEF REPORTS´ 2014 VOLUME 8 NUMBER 1
with cromolyn eye drops. Her medications during hospitalization included levothyroxine, omeprazole, metoclopramide, norethindrone/ethinyl estradiol, vitamin D, and a multivitamin. At the time of her hospitalization she was also started on total parenteral nutrition. On examination, her best-corrected visual acuity was 20/200 in the right eye and 20/70 in her left eye. The patient was unable to read any of the Ishihara color plates. Pupillary reflexes were normal bilaterally with no afferent defect. Confrontational visual fields demonstrated a constricted field in the right eye and normal fields in the left eye. Slit-lamp examination revealed moderate-to-severe superficial punctate keratopathy bilaterally. There were no bitot spots on the conjunctiva. Ophthalmoscopic examination revealed moderate pallor of the optic nerve heads bilaterally with normal maculae and periphery (Figure 1, A and B). Neurologic examination revealed intact mental status and normal cranial nerve examination. Motor examination revealed 5/5 motor strength on the right upper and lower extremities with focal areas of weakness on the left including 4/5 wrist extension, 2/5 hip flexion, 4/5 knee extension, 1/5 knee flexion, and 2/5 ankle flexion. Sensory examination identified reduced light touch sensation in the left hand, absent sensation on the left toes, decrease in temperature sensation below the knees bilaterally, and diminished vibration in bilateral lower extremities and of the left hand. Reflexes of the upper extremities were intact; however, knee and ankle reflexes were diminished bilaterally. These findings were consistent with a mixed sensory and motor neuropathy. Laboratory results showed normal serum levels of folate (19.8; normal, .4.6 ng/mL), vitamin B1 (70; range, 70–180 nmol/mL), and vitamin B12 (1683; range, 211–946 pg/mL). Serum levels for the following were: copper 40 (normal, 80–155 ug/dL), zinc 46 (normal, 60–120 ug/dL), and vitamin A ,0.06 (normal, 0.30–1.20 mg/L). Brain magnetic resonance imaging identified no compressive mass or abnormal signal or enhancement in the brain or optic nerves. A magnetic resonance imaging of the spine showed mild degenerative changes within the cervical spine but no discrete cord signal abnormality. The patients received copper and zinc through total parenteral nutrition and vitamin A 10,000 IU intramuscularly 3 days later. Follow-up examination 8 days later revealed improved vision to 20/ 20 in the right eye and 20/25 in the left eye. She saw 8/8 color plates from each eye. Ophthalmoscopic examination showed persistent optic nerve head pallor bilaterally. Optical coherence tomography of the retinal nerve fiber layer revealed mean retinal nerve fiber thickness of 87 mm in the right eye and 81 mm in the left eye with thinning seen in the inferotemporal quadrant in the right eye, and both mild nasal and temporal thinning in the left eye. A Humphrey visual field 30-2 was overall full aside from scattered
Fig. 1. Fundus photos of the right (A) and left (B) eyes with temporal disk pallor bilaterally.
deficits bilaterally 1 month after presentation (Figure 2, A and B). At 4 months, her motor and sensory upper extremity defects had resolved and lower extremity defects had improved significantly. She still had mild persistent motor weakness (4/5 and 2/5 dorsiflexion right and left, respectively) and absent vibration, temperature, and light touch sensation below the knees. Repeat laboratory values revealed normal range of serum copper and vitamin A with low zinc levels.
Discussion Obesity remains a significant and growing problem in the United States, affecting adults and children alike.1 With an increase in disease prevalence, there has been a growing trend towards bariatric surgery. Bariatric procedures are typically divided into restrictive and bypass procedures, the most popular of which is the Roux-en-Y gastric bypass. Anatomical reorganization occurring due to gastric bypass procedures can lead to malabsorption and depletion of important vitamins and minerals, such as vitamin B12, folate, zinc, copper, iron, calcium, and vitamin D.5 These nutritional deficiencies lead to a myriad of neurologic and systemic complications, such as peripheral neuropathies, encephalopathy, and optic neuropathy.1 In our patient, nutritional optic neuropathy was the leading etiologic diagnosis of her vision loss because of her history of malnutrition, bilateral loss of vision, and pale optic nerves. Common causes of nutritional deficiencies causing optic neuropathy are vitamin B12 and folate depletion that can cause a subacute onset of vision loss.6,7 In our patient, serum folate level was normal and vitamin B12 level was above normal when she began complaining of visual disturbance. Our patient was also noted to have low levels of vitamin A and had punctate epithelial keratopathy suggestive of ocular manifestation of vitamin A deficiency. However, she denied nyctalopia which is one of the earliest symptoms of vitamin A deficiency often present for weeks to months before presentation.8
NUTRITIONAL OPTIC NEUROPATHY
75
Fig. 2. Humphrey visual field (30-2) analysis showing normal mild central deficits in right eye visual field (A), and mild superior and temporal field defect in the left eye visual field (B). POS, positive; NEG, negative; GHT, Glaucoma Hemifield test; MD, mean deviation; PSD, pattern standard deviation.
Bitot spots were not noted on the conjunctiva, and systemic examination did not reveal any skin changes such as xerosis which is also seen with vitamin A deficiency. We therefore believe that it is unlikely that vitamin A deficiency alone contributed to her optic neuropathy in the absence of nyctalopia, although a multifactorial etiology with copper and vitamin A deficiency in combination causing optic neuropathy cannot be entirely ruled out. Copper plays an important component in several enzymes that are required for critical cellular processes like oxidative phosphorylation and cell metabolism. The daily allowance of copper is only 700 mg, and can be found in meats, vegetables, legumes, and whole grains.5 Copper deficiency leads to dysfunctional enzymes, particularly various oxidoreductases and monooxygenases that require copper as a cofactor.9 These copper dependent enzymes are involved in many aspects of cell metabolism including conversion of neurotransmitters, electron transport in oxidative phosphorylation, free radical scavenging, and oxidation of iron for transport.9 Copper deficiency leads to impaired metabolism of neurotransmitters and of oxidative phosphorylation that disrupts nerve conduction and affects both central and distal somatosensory pathways.10 Copper deficiency is an important cause of neuropathy in 10% to 20% of patients after GBS according to published reports.11 Our literature review revealed 5 cases of optic neuropathy occurring from copper
deficiency.11–14 Pineles et al6 described 2 cases, one was a 66-year-old woman with a history of partial gastrectomy with a progressive optic neuropathy, and the other was a 42-year-old woman with a history of GBS who developed a 1-year history of lower extremity weakness with diminished color, peripheral, and central vision. Spinazzi et al13 described the case of a 62-year-old female patient with previous Billroth II partial gastrectomy who developed progressive gait ataxia, urinary incontinence, and blurred vision. Naismith et al14 reported a 55-year-old woman with a 22-year remote history of GBS who developed an acute episode of bilateral vision loss along with progressive gait ataxia from copper deficiency. Another case by Gregg et al12 identifies a 44-year-old woman who developed optic neuropathy from copper deficiency a decade after Billroth II procedure. Improvement in visual acuity after copper replenishment was not documented in the published reports. Additionally all of the patients had a history of gastrointestinal surgery performed 7 years to 22 years before presentation. Copper absorption normally occurs from distal stomach and proximal duodenum, an area that is reduced after gastrointestinal bypass procedures.15,16 At the molecular level, a high affinity Cu1+ transporter protein on the apical surface of intestinal epithelial cells, named Ctr1, is believed to be the critical step in mineral absorption.17 Reduction in mucosal surface area causes decrease in the number of transporter
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RETINAL CASES & BRIEF REPORTS´ 2014 VOLUME 8 NUMBER 1 Table 1. Published Reports of Copper Deficiency Induced Optic Neuropathy
Cases 114 213 312 46 56 Our patient
Time From Surgery to Visual Symptoms, years 12 22 9 7 .20 ,3
Initial VA
Final VA
N/A 20/800 OU N/A 20/40 OU 20/40 OU 20/200 OD 20/80 OS
N/A N/A N/A Stabilized Stabilized 20/20 OD 20/25 OS
N/A, not available; OD, right eye; OS, left eye; OU, both eyes; VA, visual acuity.
proteins and thereby a reduction in copper absorption.18 However, Spinnazi et al13 suggest a two-hit hypothesis in which an inadequate copper intake, combined with malabsorption or excessive copper excretion, causes copper deficiency in patients with gastrointestinal surgery. In our patient, history of inadequate copper intake along with malabsorption because of altered gastric absorptive surface was possibly responsible for the rapid development of copper deficiency. We are not aware of any other case in which copper depletion caused optic neuropathy as early as 3 years after gastric bypass procedure (Table 1). In summary, although rare, copper deficiency is an important cause of optic neuropathy occurring from malnutrition. Contrary to previously published reports, copper deficiency can manifest much earlier and visual recovery is possible after mineral replenishment. Physicians should therefore have a high index of suspicion when evaluating patients with suspected malnutrition induced neurologic and ophthalmologic manifestations. We believe that serum copper levels should be routinely checked, along with vitamin B12 and folate levels, in all patients suspected of having optic neuropathy from malabsorption. Rapid recovery of vision that was observed in our patient underscores the importance of making an early diagnosis so that prompt treatment can be instituted. Key words: nutritional optic neuropathy, copper deficiency, gastric bypass surgery.
References 1. Koffman BM, Greenfield LJ, Ali II, Pirzada NA. Neurologic complications after surgery for obesity. Muscle Nerve 2006;33:166–176. 2. Livingston EH. The incidence of bariatric surgery has plateaued in the U.S. Am J Surg 2010;200:378–385. 3. Juhasz-Pocsine K, Rudnicki SA, Archer RL, Harik SI. Neurologic complications of gastric bypass surgery for morbid obesity. Neurology 2007;68:1843–1850. 4. Folope V, Coeffier M, Dechelotte P. Nutritional deficiencies associated with bariatric surgery [in French]. Gastroenterol Clin Biol 2007;31:369–377. 5. John S, Hoegerl C. Nutritional deficiencies after gastric bypass surgery. J Am Osteopath Assoc 2009;109:601–604. 6. Pineles SL, Wilson CA, Balcer LJ, et al. Combined optic neuropathy and myelopathy secondary to copper deficiency. Surv Ophthalmol 2010;55:386–392. 7. Stambolian D, Behrens M. Optic neuropathy associated with vitamin B12 deficiency. Am J Ophthalmol 1977;83:465–468. 8. Chae T, Foroozan R. Vitamin A deficiency in patients with a remote history of intestinal surgery. Br J Ophthalmol 2006;90:955–956. 9. Winston GP, Jaiser SR. Copper deficiency myelopathy and subacute combined degeneration of the cord—why is the phenotype so similar? Med Hypotheses 2008;71:229–236. 10. Goodman BP, Bosch EP, Ross MA, et al. Clinical and electrodiagnostic findings in copper deficiency myeloneuropathy. J Neurol Neurosurg Psychiatry 2009;80:524–527. 11. Gletsu-Miller N, Broderius N, Frediani JK, et al. Incidence and prevalence of copper deficiency following roux-en-y gastric bypass surgery. Int J Obes (Lond) 2012;36:328–335. 12. Gregg XT, Reddy V, Prchal JT. Copper deficiency masquerading as myelodysplastic syndrome. Blood 2002;100:1493– 1495. 13. Spinazzi M, De Lazzari F, Tavolato B, et al. Myelo-opticoneuropathy in copper deficiency occurring after partial gastrectomy. Do small bowel bacterial overgrowth syndrome and occult zinc ingestion tip the balance? J Neurol 2007;254:1012– 1017. 14. Naismith RT, Shepherd JB, Weihl CC, et al. Acute and bilateral blindness due to optic neuropathy associated with copper deficiency. Arch Neurol 2009;66:1025–1027. 15. Sternlieb I, Janowitz HD. Absorption of copper in malabsorption syndromes. J Clin Invest 1964;43:1049–1055. 16. Van Campen DR. Effects of zinc, cadmium, silver and mercury on the absorption and distribution of copper-64 in rats. J Nutr 1966;88:125–130. 17. Kim BE, Nevitt T, Thiele DJ. Mechanisms for copper acquisition, distribution and regulation. Nat Chem Biol 2008;4:176–185. 18. Wapnir RA. Copper absorption and bioavailability. Am J Clin Nutr 1998;67:1054S–1060S.
Purpose: Patients undergoing gastric bypass procedures are predisposed to many vitamin and mineral deficiencies including copper, which can lead to optic neuropathy. Methods: A 35-year-old woman complained of progressive vision loss bilaterally 3 years after gastric bypass surgery (GBS). Results: Ophthalmic examination revealed the presence of subnormal visual acuity and pale optic nerves bilaterally. Laboratory testing showed copper deficiency. Complete improvement in vision was noted after copper was replenished. Conclusion: Nutritional deficiencies occurring after gastric bypass procedures are well reported. They happen and occur due to reduced gastric and enteral absorption and cause many systemic and neurologic manifestations. Optic neuropathy occurring after GBS is often due to vitamin B12 and folic acid deficiency. Copper deficiency causing systemic symptoms is very rare and usually takes decades to manifest. Our case is unique in that copper deficiency was noted as early as 3 years after GBS. Moreover rapid copper replenishment led to a dramatic recovery of vision. Our case underscores the need for maintaining high suspicion when evaluating patients with suspected optic neuropathy occurring after GBS since prompt diagnosis and treatment may lead to reversal of visual loss. RETINAL CASES & BRIEF REPORTS 8:73–76, 2014
lopathy, myopathy, and encephalopathy have been described3 that occur from nutritional deficiency of fatsoluble vitamins, folic acid, and zinc.4 Our patient, diagnosed with copper deficiency developed progressive visual decline 3 years after GBS. To the best of our knowledge, an early onset of copper deficiency as seen in our patient and a rapid recovery of vision noted after copper replenishment, have previously not been reported. Our case highlights the need for a high index of suspicion, which allows for prompt clinical diagnosis and treatment.
From the Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania.
O
besity is an epidemic in the United States with over 25% of adults and children clinically obese.1 The number of bariatric surgeries performed in the United States has steadily increased with 113,000 cases being performed annually.2 Patients who undergo gastric bypass surgery (GBS) are predisposed to many vitamin and mineral deficiencies secondary to gastric anatomical rearrangement. Numerous neurologic complications including polyneuropathy, mye-
Case Report Supported by Research to Prevent Blindness, Inc, New York, NY, that provided travel support. Paper presented as a poster at the North American NeuroOphthalmologic Society Meeting, San Antonio, TX, February 2012. None of the authors have any conflicting interests to disclose. Reprint requests: Madhura Tamhankar, MD, Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, 51 N. 39th Street, Philadelphia, PA 19104; e-mail: madhura. [email protected]
A 35-year-old woman presented with progressive systemic weakness, dizziness, and frequent falling over a 9-month period. One month before admission, the patient noted nausea, vomiting, peripheral edema without orthopnea, and lower extremity pain. Her medical history was significant for having undergone a Roux-en-Y GBS 3 years ago. She was taking an oral multivitamin before hospital admission. While in the hospital, the patient complained of progressively worsening vision bilaterally for 2 weeks. She denied night blindness. Her ocular history included ocular allergies treated
73
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RETINAL CASES & BRIEF REPORTS´ 2014 VOLUME 8 NUMBER 1
with cromolyn eye drops. Her medications during hospitalization included levothyroxine, omeprazole, metoclopramide, norethindrone/ethinyl estradiol, vitamin D, and a multivitamin. At the time of her hospitalization she was also started on total parenteral nutrition. On examination, her best-corrected visual acuity was 20/200 in the right eye and 20/70 in her left eye. The patient was unable to read any of the Ishihara color plates. Pupillary reflexes were normal bilaterally with no afferent defect. Confrontational visual fields demonstrated a constricted field in the right eye and normal fields in the left eye. Slit-lamp examination revealed moderate-to-severe superficial punctate keratopathy bilaterally. There were no bitot spots on the conjunctiva. Ophthalmoscopic examination revealed moderate pallor of the optic nerve heads bilaterally with normal maculae and periphery (Figure 1, A and B). Neurologic examination revealed intact mental status and normal cranial nerve examination. Motor examination revealed 5/5 motor strength on the right upper and lower extremities with focal areas of weakness on the left including 4/5 wrist extension, 2/5 hip flexion, 4/5 knee extension, 1/5 knee flexion, and 2/5 ankle flexion. Sensory examination identified reduced light touch sensation in the left hand, absent sensation on the left toes, decrease in temperature sensation below the knees bilaterally, and diminished vibration in bilateral lower extremities and of the left hand. Reflexes of the upper extremities were intact; however, knee and ankle reflexes were diminished bilaterally. These findings were consistent with a mixed sensory and motor neuropathy. Laboratory results showed normal serum levels of folate (19.8; normal, .4.6 ng/mL), vitamin B1 (70; range, 70–180 nmol/mL), and vitamin B12 (1683; range, 211–946 pg/mL). Serum levels for the following were: copper 40 (normal, 80–155 ug/dL), zinc 46 (normal, 60–120 ug/dL), and vitamin A ,0.06 (normal, 0.30–1.20 mg/L). Brain magnetic resonance imaging identified no compressive mass or abnormal signal or enhancement in the brain or optic nerves. A magnetic resonance imaging of the spine showed mild degenerative changes within the cervical spine but no discrete cord signal abnormality. The patients received copper and zinc through total parenteral nutrition and vitamin A 10,000 IU intramuscularly 3 days later. Follow-up examination 8 days later revealed improved vision to 20/ 20 in the right eye and 20/25 in the left eye. She saw 8/8 color plates from each eye. Ophthalmoscopic examination showed persistent optic nerve head pallor bilaterally. Optical coherence tomography of the retinal nerve fiber layer revealed mean retinal nerve fiber thickness of 87 mm in the right eye and 81 mm in the left eye with thinning seen in the inferotemporal quadrant in the right eye, and both mild nasal and temporal thinning in the left eye. A Humphrey visual field 30-2 was overall full aside from scattered
Fig. 1. Fundus photos of the right (A) and left (B) eyes with temporal disk pallor bilaterally.
deficits bilaterally 1 month after presentation (Figure 2, A and B). At 4 months, her motor and sensory upper extremity defects had resolved and lower extremity defects had improved significantly. She still had mild persistent motor weakness (4/5 and 2/5 dorsiflexion right and left, respectively) and absent vibration, temperature, and light touch sensation below the knees. Repeat laboratory values revealed normal range of serum copper and vitamin A with low zinc levels.
Discussion Obesity remains a significant and growing problem in the United States, affecting adults and children alike.1 With an increase in disease prevalence, there has been a growing trend towards bariatric surgery. Bariatric procedures are typically divided into restrictive and bypass procedures, the most popular of which is the Roux-en-Y gastric bypass. Anatomical reorganization occurring due to gastric bypass procedures can lead to malabsorption and depletion of important vitamins and minerals, such as vitamin B12, folate, zinc, copper, iron, calcium, and vitamin D.5 These nutritional deficiencies lead to a myriad of neurologic and systemic complications, such as peripheral neuropathies, encephalopathy, and optic neuropathy.1 In our patient, nutritional optic neuropathy was the leading etiologic diagnosis of her vision loss because of her history of malnutrition, bilateral loss of vision, and pale optic nerves. Common causes of nutritional deficiencies causing optic neuropathy are vitamin B12 and folate depletion that can cause a subacute onset of vision loss.6,7 In our patient, serum folate level was normal and vitamin B12 level was above normal when she began complaining of visual disturbance. Our patient was also noted to have low levels of vitamin A and had punctate epithelial keratopathy suggestive of ocular manifestation of vitamin A deficiency. However, she denied nyctalopia which is one of the earliest symptoms of vitamin A deficiency often present for weeks to months before presentation.8
NUTRITIONAL OPTIC NEUROPATHY
75
Fig. 2. Humphrey visual field (30-2) analysis showing normal mild central deficits in right eye visual field (A), and mild superior and temporal field defect in the left eye visual field (B). POS, positive; NEG, negative; GHT, Glaucoma Hemifield test; MD, mean deviation; PSD, pattern standard deviation.
Bitot spots were not noted on the conjunctiva, and systemic examination did not reveal any skin changes such as xerosis which is also seen with vitamin A deficiency. We therefore believe that it is unlikely that vitamin A deficiency alone contributed to her optic neuropathy in the absence of nyctalopia, although a multifactorial etiology with copper and vitamin A deficiency in combination causing optic neuropathy cannot be entirely ruled out. Copper plays an important component in several enzymes that are required for critical cellular processes like oxidative phosphorylation and cell metabolism. The daily allowance of copper is only 700 mg, and can be found in meats, vegetables, legumes, and whole grains.5 Copper deficiency leads to dysfunctional enzymes, particularly various oxidoreductases and monooxygenases that require copper as a cofactor.9 These copper dependent enzymes are involved in many aspects of cell metabolism including conversion of neurotransmitters, electron transport in oxidative phosphorylation, free radical scavenging, and oxidation of iron for transport.9 Copper deficiency leads to impaired metabolism of neurotransmitters and of oxidative phosphorylation that disrupts nerve conduction and affects both central and distal somatosensory pathways.10 Copper deficiency is an important cause of neuropathy in 10% to 20% of patients after GBS according to published reports.11 Our literature review revealed 5 cases of optic neuropathy occurring from copper
deficiency.11–14 Pineles et al6 described 2 cases, one was a 66-year-old woman with a history of partial gastrectomy with a progressive optic neuropathy, and the other was a 42-year-old woman with a history of GBS who developed a 1-year history of lower extremity weakness with diminished color, peripheral, and central vision. Spinazzi et al13 described the case of a 62-year-old female patient with previous Billroth II partial gastrectomy who developed progressive gait ataxia, urinary incontinence, and blurred vision. Naismith et al14 reported a 55-year-old woman with a 22-year remote history of GBS who developed an acute episode of bilateral vision loss along with progressive gait ataxia from copper deficiency. Another case by Gregg et al12 identifies a 44-year-old woman who developed optic neuropathy from copper deficiency a decade after Billroth II procedure. Improvement in visual acuity after copper replenishment was not documented in the published reports. Additionally all of the patients had a history of gastrointestinal surgery performed 7 years to 22 years before presentation. Copper absorption normally occurs from distal stomach and proximal duodenum, an area that is reduced after gastrointestinal bypass procedures.15,16 At the molecular level, a high affinity Cu1+ transporter protein on the apical surface of intestinal epithelial cells, named Ctr1, is believed to be the critical step in mineral absorption.17 Reduction in mucosal surface area causes decrease in the number of transporter
76
RETINAL CASES & BRIEF REPORTS´ 2014 VOLUME 8 NUMBER 1 Table 1. Published Reports of Copper Deficiency Induced Optic Neuropathy
Cases 114 213 312 46 56 Our patient
Time From Surgery to Visual Symptoms, years 12 22 9 7 .20 ,3
Initial VA
Final VA
N/A 20/800 OU N/A 20/40 OU 20/40 OU 20/200 OD 20/80 OS
N/A N/A N/A Stabilized Stabilized 20/20 OD 20/25 OS
N/A, not available; OD, right eye; OS, left eye; OU, both eyes; VA, visual acuity.
proteins and thereby a reduction in copper absorption.18 However, Spinnazi et al13 suggest a two-hit hypothesis in which an inadequate copper intake, combined with malabsorption or excessive copper excretion, causes copper deficiency in patients with gastrointestinal surgery. In our patient, history of inadequate copper intake along with malabsorption because of altered gastric absorptive surface was possibly responsible for the rapid development of copper deficiency. We are not aware of any other case in which copper depletion caused optic neuropathy as early as 3 years after gastric bypass procedure (Table 1). In summary, although rare, copper deficiency is an important cause of optic neuropathy occurring from malnutrition. Contrary to previously published reports, copper deficiency can manifest much earlier and visual recovery is possible after mineral replenishment. Physicians should therefore have a high index of suspicion when evaluating patients with suspected malnutrition induced neurologic and ophthalmologic manifestations. We believe that serum copper levels should be routinely checked, along with vitamin B12 and folate levels, in all patients suspected of having optic neuropathy from malabsorption. Rapid recovery of vision that was observed in our patient underscores the importance of making an early diagnosis so that prompt treatment can be instituted. Key words: nutritional optic neuropathy, copper deficiency, gastric bypass surgery.
References 1. Koffman BM, Greenfield LJ, Ali II, Pirzada NA. Neurologic complications after surgery for obesity. Muscle Nerve 2006;33:166–176. 2. Livingston EH. The incidence of bariatric surgery has plateaued in the U.S. Am J Surg 2010;200:378–385. 3. Juhasz-Pocsine K, Rudnicki SA, Archer RL, Harik SI. Neurologic complications of gastric bypass surgery for morbid obesity. Neurology 2007;68:1843–1850. 4. Folope V, Coeffier M, Dechelotte P. Nutritional deficiencies associated with bariatric surgery [in French]. Gastroenterol Clin Biol 2007;31:369–377. 5. John S, Hoegerl C. Nutritional deficiencies after gastric bypass surgery. J Am Osteopath Assoc 2009;109:601–604. 6. Pineles SL, Wilson CA, Balcer LJ, et al. Combined optic neuropathy and myelopathy secondary to copper deficiency. Surv Ophthalmol 2010;55:386–392. 7. Stambolian D, Behrens M. Optic neuropathy associated with vitamin B12 deficiency. Am J Ophthalmol 1977;83:465–468. 8. Chae T, Foroozan R. Vitamin A deficiency in patients with a remote history of intestinal surgery. Br J Ophthalmol 2006;90:955–956. 9. Winston GP, Jaiser SR. Copper deficiency myelopathy and subacute combined degeneration of the cord—why is the phenotype so similar? Med Hypotheses 2008;71:229–236. 10. Goodman BP, Bosch EP, Ross MA, et al. Clinical and electrodiagnostic findings in copper deficiency myeloneuropathy. J Neurol Neurosurg Psychiatry 2009;80:524–527. 11. Gletsu-Miller N, Broderius N, Frediani JK, et al. Incidence and prevalence of copper deficiency following roux-en-y gastric bypass surgery. Int J Obes (Lond) 2012;36:328–335. 12. Gregg XT, Reddy V, Prchal JT. Copper deficiency masquerading as myelodysplastic syndrome. Blood 2002;100:1493– 1495. 13. Spinazzi M, De Lazzari F, Tavolato B, et al. Myelo-opticoneuropathy in copper deficiency occurring after partial gastrectomy. Do small bowel bacterial overgrowth syndrome and occult zinc ingestion tip the balance? J Neurol 2007;254:1012– 1017. 14. Naismith RT, Shepherd JB, Weihl CC, et al. Acute and bilateral blindness due to optic neuropathy associated with copper deficiency. Arch Neurol 2009;66:1025–1027. 15. Sternlieb I, Janowitz HD. Absorption of copper in malabsorption syndromes. J Clin Invest 1964;43:1049–1055. 16. Van Campen DR. Effects of zinc, cadmium, silver and mercury on the absorption and distribution of copper-64 in rats. J Nutr 1966;88:125–130. 17. Kim BE, Nevitt T, Thiele DJ. Mechanisms for copper acquisition, distribution and regulation. Nat Chem Biol 2008;4:176–185. 18. Wapnir RA. Copper absorption and bioavailability. Am J Clin Nutr 1998;67:1054S–1060S.
